U.S. Pat. No. 4,341,784 issued on July 27, 1982 discloses the following compounds with antibacterial activity. ##STR3## wherein R is methyl, ethyl or propyl.
But the compounds of this invention are surprisingly superior to the above known compounds in their antibacterial activity as shown hereinafter.
On the other hand, U.S. Pat. No. 4,382,937 issued on May 10, 1983 discloses that compounds in which the ethyl group of the 1-position of 1,8-naphthyridine of the foregoing formula has been converted to the vinyl group have antibacterial activity.
European Laid-Open Patent Specification No. 49355 published on Apr. 4, 1982 discloses the following general formula ##STR4##
In regard to the group ##STR5## shown in this formula, there is however no disclosure at all as to whether this is an amino-substituted pyrrolidinyl group and an amino and alkyl-substituted pyrrolidinyl group.
It is an object of the invention to provide novel 1,8-naphthyridine compounds (I) having high antibacterial activities against both Gram-positive bacteria and Gram-negative bacteria, as well as esters and pharmaceutically acceptable salts thereof, and processes for preparing these novel compounds.
Another object of the invention is to provide a pharmaceutical composition which contains an antibacterially effective amount of a compound selected from compounds having the structural formula (I), esters and pharmaceutically acceptable salts thereof.
The invention further provides a method for treating bacterial infectious diseases which comprises administering to warm-blooded animals an antibacterially effective amount of the compound of this invention or the aforesaid pharmaceutical composition.
These and other objects of the invention will become apparent from the following description.
The compounds of the invention represented by formula (I) include as preferred compounds the following. 7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-na phthyridine-3-carboxylic acid (hereinafter referred to as compound 1), ##STR6##
1-Cyclopropyl-6-fluoro-7-(3-methylamino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1 ,8-naphthyridine-3-carboxylic acid (hereinafter referred to as compound 2), ##STR7##
1-Cyclopropyl-7-(3-ethylamino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid, ##STR8##
7-(3-Amino-2-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-ox o-1,8-naphthyridine-3-carboxylic acid. ##STR9## 7-(3-Amino-4-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-o x o-1,8-naphthyridine-3-carboxylic acid (hereinafter referred to as compound 3),
7-(3-Amino-3-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-ox o-1,8-naphthyridine-3-carboxylic acid (hereinafter referred to as compound 4), ##STR10##
7-(3-Amino-4-ethyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo -1,8-naphthyridine-3-carboxylic acid, ##STR11##
7-(4-Amino-2-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-ox o-1,8-naphthyridine-3-carboxylic acid, ##STR12##
7-(3-Amino-4,4-dimethyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid, ##STR13##
1-cyclopropyl-6-fluoro-7-(3-methyl-4-methylamino-1-pyrrolidinyl)-1,4-dihydr o-4-oxo-1,8-naphthyridine-3-carboxylic acid, ##STR14##
The lower alkyl esters having 1 to 5 carbon atoms of the above compounds and the pharmaceutically acceptable acid addition salts of these compounds, such as the hydrochlorides and methanesulfonates, are also suitable.
Of these compounds, especially to be preferred are the following:
7-(3-Amino-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-nap hthyridine-3-carboxylic acid (Compound 1), PA0 1-Cyclopropyl-6-fluoro-7-(3-methylamino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1 ,8-naphthyridine-3-carboxylic acid (Compound 2), PA0 7-(3-Amino-4-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-ox o-1,8-naphthyridine-3-carboxylic acid (Compound 3), PA0 7-(3-Amino-3-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-ox o-1,8-naphthyridine-3-carboxylic acid (Compound 4),
and the hydrochlorides and the lower alkyl esters having 1 to 3 carbon atoms of the above compounds.